Picroside II ameliorates Aβ-induced memory deficit by enhancing autophagy in mice

Abstract Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by the accumulation of misfolded amyloid-β (Aβ) peptides, which is caused by an imbalance between Aβ production and clearance. Picroside II (Picr II), the principal active constituent of Picrorhizakurroa Royle ex Benth, possesses a range of pharmacological properties, such as anti-inflammatory, antioxidant, and antiapoptotic effects. However, the exact role of Picr II in AD is not yet fully understood. In this study, we investigated the effects of Picr II on AD and found that it inhibited amyloid precursor protein (APP) processing by enhancing autophagy rather than through the ubiquitin-proteasome pathway, resulting in a reduction in Aβ production. Furthermore, Picr II treatment improved the decline in autophagy, which was due not only to an increase in autophagic flux but also to an increase in the fusion of autophagosomes with lysosomes. Most importantly, daily treatment with Picr II (20 mg/kg, i.p.) throughout the experiment rescued the learning and memory in Aβ-treated mice. Taken together, these results suggest that Picr II may have a potent neuroprotective effect against Aβ-induced memory decline by enhancing autophagy, indicating that Picr II may be a promising therapeutic agent for AD.